LAUSR

OBJECTIVE Long noncoding RNAs (lncRNA) play a crucial role in the process of immune-mediated diseases. However, the defined involvement of lncRNA on Behcet's disease (BD) is not well known. The aim of this study was to investigate the effects of lncRNA-related single nucleotide polymorphisms (SNPs) on BD susceptibility in Chinese populations. METHODS A two-stage case-control association study was conducted in a cohort of 1152 BD individuals and 1152 healthy controls. Genotyping was performed by MassARRAY System. Quantified expression of lncRNA-miRNA-mRNA molecular axis were detected by real-time PCR and western blot. The cell proliferation was measured by CCK-8 assay. RESULTS Two-stage association analysis showed a significantly decreased frequency of A allele of SNP rs7130280 in BD patients compared with healthy controls (OR = 0.72, 95% CI = 0.64-0.81, Pc=1.15 × 1 0 -6). Functionally, SNP rs7130280 could influence the secondary structure and relative expression of NONHSAT159216.1 in human THP-1/U937 macrophages and in peripheral blood mononuclear cells from healthy volunteers. In vitro, overexpression of the rs7130280 A allele also suppressed cell proliferation. Mechanistically, rs7130280 A allele could inhibit the expression of miR-6778-5p, thus enhanced its downstream molecular RPS6KA4/IL10 in a ceRNA sponge manner. CONCLUSION Our findings suggest that NONHSAT159216.1 rs7130280 G > A might be associated with low risk of BD and participates in a potential lncRNA-miRNA-mRNA regulatory network.